A Study of TBio-4101 (TIL) and Pembrolizumab in Patients With Advanced Solid Tumors

NCT05576077 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: TBio-4101-001
• Study Type: interventional
• Target: 31
• Locations: 2 countries
• Sites: 13

Brief Summary

A multicenter trial to investigate TBio-4101, an autologous, neoantigen-selected, tumor-reactive TIL product, in patients with advanced solid malignancies.

Conditions

Breast Cancer; Colorectal Cancer; Uveal Melanoma; Cutaneous Melanoma; Non-Small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma

Keywords

MSS-CRC; TIL; Tumor infiltrating lymphocyte; TNBC; HR+ Breast; ER+ Breast; MSI-CRC; personalized medicine; ocular melanoma

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability

  The incidence of treatment-emergent adverse events will be tabulated using NCI CTCAE v5.0

  25 months

Secondary Outcomes (3)

• Proportion of patients with a response (ORR)

  25 months

• Estimated Disease Control Rate (DCR)

  25 months

• Estimated Duration of Response (DoR)

  25 months

Study Arms (6)

Breast Cancer

EXPERIMENTAL

Patients with locally advanced or metastatic breast cancer that has failed or is intolerant to standard of care therapies. Includes, HER2+, HER 2-, TNBC.

Biological: TBio-4101; Drug: Pembrolizumab

Colorectal carcinoma

EXPERIMENTAL

Patients with advanced, metastatic colorectal adenocarcinoma who have failed or are intolerant to at least one line of therapy that included either irinotecan or oxaliplatin.

Biological: TBio-4101; Drug: Pembrolizumab

Uveal Melanoma

EXPERIMENTAL

Patients with advanced, metastatic uveal melanoma.

Biological: TBio-4101; Drug: Pembrolizumab

Cutaneous Melanoma

EXPERIMENTAL

Patients with cutaneous melanoma who have experienced disease progression following a PD-1 or PD-L1 inhibitor.

Biological: TBio-4101; Drug: Pembrolizumab

Non-Small Cell Lung Cancer

EXPERIMENTAL

Patients with non-small cell lung cancer who have experienced disease progression following platinum containing chemotherapy and/or PD-1 or PD-L1 inhibitor.

Biological: TBio-4101; Drug: Pembrolizumab

Head and Neck Squamous Cell Carcinoma

EXPERIMENTAL

* Patients with head and neck squamous cell carcinoma who have received no prior therapy for metastatic disease * Patients with head and neck squamous cell carcinoma who are PD-1/PD-L1 inhibitor naïve at the time of TIL harvest and will be treated with TBio-4101 at the time of progression, inadequate response or intolerance to the PD-1/PD-L1 inhibitor-based standard of care regimen given on study.

Biological: TBio-4101; Drug: Pembrolizumab

Interventions

TBio-4101 BIOLOGICAL

TBio-4101 is an autologous selected and expanded tumor infiltrating lymphocyte (TIL) product generated following ex vivo expansion of tumor reactive TIL population found in tumor harvest. After preparation with non-myeloablative lymphodepletion chemotherapy (cyclophosphamide and fludarabine) followed by low dose radiation,TBio-4101, and IL-2.

Also known as: TIL, autologous, tumor-reactive, T-cell product

Breast Cancer; Colorectal carcinoma; Cutaneous Melanoma; Head and Neck Squamous Cell Carcinoma; Non-Small Cell Lung Cancer; Uveal Melanoma

Pembrolizumab DRUG

Pembrolizumab will be administered after TIL infusion and continue every 3-6 weeks for up to 2 years.

Also known as: Keytruda

Breast Cancer; Colorectal carcinoma; Cutaneous Melanoma; Head and Neck Squamous Cell Carcinoma; Non-Small Cell Lung Cancer; Uveal Melanoma

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Advanced or metastatic breast carcinoma, colorectal adenocarcinoma, uveal melanoma, cutaneous melanoma, non-small cell lung cancer, or head and neck squamous cell carcinoma that has failed or is refractory to standard of care therapy
• Have at least one target lesion that can be used for response assessments and have at least 1 tumor amenable for tissue harvest for TIL manufacturing.
• ECOG performance status of 0 or 1
• Demonstrate adequate organ function

You may not qualify if:

• Known additional malignancy that is progressing or has required active treatment within the past 3 years
• Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy or any other form of immunosuppressive
• Currently infected with HIV Type 1 and Type 2, hepatitis B virus (HBV), hepatitis C virus (HCV), treponema pallidum (e.g., syphilis), West Nile virus (WNV), Human T-lymphotropic virus types 1 or II (HTLV I/II), or cytomegalovirus (CMV)
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable
• Serious cardiac condition, such as uncontrolled hypertension, concurrent congestive heart failure, prior history of Class III/IV cardiac disease (New York Heart Association \[NYHA\]), history of cardiac ischemia within the past 6 months, or prior history of cardiac arrhythmia requiring treatment. Patients who are \> 60 years of age must undergo cardiology clearance exam and cardiac stress test.
• Prior cell therapy or organ transplant
• History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, IL-2, or pembrolizumab, or any of their constituents
• LVEF ≤ 45%
• FEV1 ≤ 60% of predicted value and DLCO (corrected) \< 60% of predicted value
• Chronic anti-coagulant therapy that cannot either be discontinued or temporarily changed

Sponsors & Collaborators

• Turnstone Biologics, Corp.: lead

Study Sites (13)

University of California Irvine

Irvine, California, 92868, United States

Location

Memorial Healthcare System

Hollywood, Florida, 33021, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Orlando Health

Orlando, Florida, 32806, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612-9497, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

Location

Providence Cancer Institute

Portland, Oregon, 97213, United States

Location

Allegheny Research Institute

Pittsburgh, Pennsylvania, 15224, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2C1, Canada

Location

Montreal University Hospital Center

Montreal, Quebec, H2X 0C1, Canada

Location

MeSH Terms

Conditions

Breast Neoplasms; Colorectal Neoplasms; Uveal Melanoma; Melanoma; Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck

Interventions

Toll-Like Receptor 1; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal Diseases; Skin Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms

Intervention Hierarchy (Ancestors)

Toll-Like Receptors; Receptors, Pattern Recognition; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Ines Verdon, MD

  Turnstone Biologics, Corp.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients enrolled into a Cohort based on malignancy.

Study Record Dates

• First Submitted: October 7, 2022
• First Posted: October 12, 2022
• Study Start: January 17, 2023
• Primary Completion: February 4, 2025
• Study Completion: February 24, 2025
• Last Updated: March 10, 2025

Record last verified: 2025-03

Locations

US (11); CA (2)